Construction of micropapillary lung adenocarcinoma organoids and screening of targeted drugs / 天津医药

Objective To establish a culture method for micropapillary lung adenocarcinoma organoids and conduct targeted drug screening.Methods Organoids were extracted and cultured from a surgical tissue sample of a patient diagnosed with micropapillary lung adenocarcinoma,and the growth of lung cancer organoids was observed and recorded dynamically.The morphological and gene expression characteristics of tumor cells between lung cancer organoids and parental tissue were compared using hematoxylin eosin(HE)staining and immunohistochemical methods.Real time fluorescence quantitative polynucleotide chain reaction(qRT-PCR)method was used to detect gene mutations in lung cancer parental tissue and organoids.Finally,based on results of genetic testing,targeted drugs were selected and their therapeutic effects were verified.Results We have successfully cultured spherical organoids from micropapillary lung adenocarcinoma tissue,which can be passaged for at least 3 generations.HE staining results showed that the morphology of tumor cells in organoids was roughly consistent with that of parental tissue.The immunohistochemical results showed that the protein expression levels of various genes in lung cancer organoids and parental tissue were roughly the same.Results of gene mutation analysis showed that the mutated genes in lung cancer parental tissue and organoids were consistent,both reflecting RET fusion.The screening results of targeted drugs based on lung cancer organoids showed that vandertinib had the best anti-tumor effect in vitro.Conclusion Drug screening experiments based on micropapillary lung adenocarcinoma organoids can screen highly efficient targeted drugs in a short period of time,which may benefit patients with micropapillary lung adenocarcinoma.

A clinical prediction model based on 68Ga-PSMA-11 PET/CT and mpMRI parameters to determine the diagnostic accuracy of targeted biopsy alone in prostate cancer population / 现代泌尿外科杂志

【Objective】 To develop a clinical prediction model based on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA-11), positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) parameters to stratify prostate cancer patients undergoing targeted biopsy, so as to avoid unnecessary systematic biopsy. 【Methods】 A total of 96 clinically significant prostate cancer (csPCa) patients who underwent 68Ga-PSMA-11 PET/CT and mpMRI prior to prostate targeted biopsy with systematic biopsy during Jan.2020 and Feb.2023 in Nanjing Drum Tower Hospital were retrospectively analyzed.By univariate and multivariate logistic regression analyses, maximum standard uptake value (SUVmax) in 68Ga-PSMA-11 PET/CT and minimum apparent diffusion coefficien (ADCmin) in mpMRI, as well as clinical parameters were evaluated to identify the independent predictors correlative with the effective diagnosis of targeted biopsy, and a clinical prediction model was constructed. 【Results】 Multivariate logistic regression analysis showed that SUVmax (OR=0.878, 95%CI: 0.804-0.959, P=0.004) and ADCmin (OR=1.005, 95%CI:1.001-1.010, P=0.027) were independent predictors of the effective diagnosis of targeted biopsy alone.The sensitivity, specificity, accuracy and area under the receiver operator characteristic curve (AUC) of the model were 0.80, 0.80, 0.83 and 0.84, respectively. 【Conclusion】 The clinical prediction model based on 68Ga-PSMA-11 PET/CT and mpMRI parameters is helpful to improve the effective diagnosis of targeted biopsy alone, and has practical value to stratify patients with csPCa so as to safely avoid systematic biopsy and effectively balance the benefits and risks.

Polyene phosphatidylcholine injection in the treatment of alcoholic liver disease:a systematic review and Meta-analysis / 中国药师

Objective To evaluate the efficacy and safety of polyene phosphatidylcholine injection in the treatment of liver disease.Methods Pubmed,Embase,The Cochrane Library,ClinicalTrial.gov,CNKI,SinoMed,VIP,and WanFang Data were electronically searched to collect randomized controlled trials(RCTs)of polyene phosphatidylcholine injection in the treatment of liver disease from inception to December 31st,2022.Two researchers independently screened literature,extracted data and assessed the risk of bias of the included studies.The Meta-analysis was performed using Stata 17.0 software.Results A total of 10 RCTs were included,including 809 patients.Meta-analysis showed that the effective rate in the polyene phosphatidylcholine injection group was higher than that in the control group(RR=1.12,95％CI 1.04 to 1.20,P=0.003 8).Compared with the control group,polyene phosphatidylcholine injection could decrease ALT level(MD=-18.92 U/L,95％CI-27.75 to-10.09,P＜0.001),AST level(MD=-31.19 U/L,95％CI-46.27 to-16.11,P=0.000 1),TBiL level(MD=-7.31 μmol/L,95％CI-10.75 to-3.88,P＜0.001),and GGT levels(MD=-48.93 U/L,95％CI-54.64 to-43.21,P＜0.001).Only one study reported mild adverse events,and six studies reported no severe adverse events in patients.Conclusion Current evidence shows that polyene phosphatidylcholine injection in the treatment of alcoholic liver disease can increase the effective rate,improve the levels of liver function indicators(ALT,AST,TBiL,and GGT),and has less adverse events.Due to the limited number and quality of included studies,the above conclusions need to be verified by more high-quality studies.

A prospective study of the perforator evaluation and eccentric design of anterolateral thigh flap based on superficial fascial perforators assisted by modified computed tomography angiography / 中华烧伤杂志

Objective: To explore the preoperative whole perforator evaluation and intraoperative eccentric design of anterolateral thigh flap (ALTF) based on superficial fascial perforators by modified computed tomography angiography (CTA), and the clinical effects were observed. Methods: A prospective observational study was adopted. Twelve patients with oral and maxillofacial tumors and 10 patients with open injury of the upper limb with large soft tissue defects were hospitalized in the Department of Hand & Microsurgery and Department of Oral & Maxillofacial Surgery of Affiliated Hospital of Binzhou Medical University from January 2021 to July 2022, with 12 males and 10 females, aged from 33 to 75 years, an average age of 56.6 years. The wounds of the patients with oral and maxillofacial tumors were reconstructed by ALTF after the extensive tumor resection and radical cervical lymph node dissection in the same stage; the wounds of the patients with skin and soft tissue defect on the upper limb were covered by ALTF in stage Ⅱ after debridement in stage Ⅰ. After debridement, the area of wound was 3.5 cm×3.5 cm-25.0 cm×10.0 cm and the area of the required flap area was 4.0 cm×4.0 cm-23.0 cm×13.0 cm. Modified CTA scan was performed on the donor site of ALTF before the operation, with the parameters of modified CTA being set to mainly reduce the tube voltage and tube current, and increase the contrast dose and the dual phase scan. The acquired image data were sent to GE AW 4.7 workstation and adopted the volume reconstruction function for visual reconstruction and evaluation of the whole perforator. The information of perforator and source artery was marked on the body surface before operation according to the above evaluation. During the operation, an eccentric flap centered on the visible superficial fascia whole perforator was designed and cut according to the desired flap area and shape. The donor sites of the flap were repaired by direct sutures or full-thickness skin grafts. The total radiation dose was compared between the modified CTA scan and the traditional CTA scan. The distribution of outlet point of perforator of double thighs, the length and direction of superficial fascia perforators based modified CTA were recorded. The type, number, and origin of the target perforator, distribution of of outlet point of perforator, and the diameter, course, and branch of the source artery observed before the operation were compared with those observed during the operation. The healing of donor site wound and the survival of flaps in recipient site were observed after operation. The texture and appearance of flap, oral and upper limb functions, and the functions of femoral donor sites were followed up. Results: The total radiation dose of modified CTA scan was lower than that of the traditional CTA scan. A total of 48 perforators of double thighs were observed, among which, 31 (64.6%) perforators went outward and downward, 9 (18.8%) perforators went inward and downward, 6 (12.5%) perforators went outward and upward, and 2 (4.2%) perforators went inward and upward, and the average length of superficial fascia perforators was 19.94 mm. The preoperative observed type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery were basically consistent with the intraoperative exploration. The types of 15 septocutaneous (including musculoseptocutaneous) perforators and 10 musculocutaneous perforators observed before the operation was consistent with intraoperative exploration. The distance between the mark of the surface perforator point and the actual exit point of the perforator during operation was (0.38±0.11) mm. All flaps survived without vascular crisis. The donor site wounds of 5 cases of skin grafting and 17 cases of direct suturing wounds healed well. The postoperative follow-up was 2 months to 1 year, with an average of 8.2 months, the flaps were soft and slightly bloated; the function of diet and mouth closing was accessible in patients with oral and maxillofacial tumors, the speech function was mildly impaired in patients with tongue cancer, but they could complete basic oral communication; the wrist and elbow joints and forearm rotation function were not significantly limited in patients with upper limb soft tissue injuries; there was no obvious tightness in the donor sites, and the function of the hip and knee joints was not limited. Conclusions: The whole perforator and even the subcutaneous perforator of the donor site of ALTF can be evaluated by modified CTA, and the flap can be used in oral or maxillofacial reconstruction and repair of skin and soft tissue defects of upper limbs to achieve good results. By clarifying the type, number, and source of the perforator, the distribution of the outlet point of the perforator, diameter, course, and branches of the source artery before the operation, the eccentric design of the ALTF based on the superficial fascia perforator was realized. This study has strong guiding value.

Recent advances in bacterial therapeutics based on sense and response

Intelligent drug delivery is a promising strategy for cancer therapies. In recent years, with the rapid development of synthetic biology, some properties of bacteria, such as gene operability, excellent tumor colonization ability, and host-independent structure, make them ideal intelligent drug carriers and have attracted extensive attention. By implanting condition-responsive elements or gene circuits into bacteria, they can synthesize or release drugs by sensing stimuli. Therefore, compared with traditional drug delivery, the usage of bacteria for drug loading has better targeting ability and controllability, and can cope with the complex delivery environment of the body to achieve the intelligent delivery of drugs. This review mainly introduces the development of bacterial-based drug delivery carriers, including mechanisms of bacterial targeting to tumor colonization, gene deletions or mutations, environment-responsive elements, and gene circuits. Meanwhile, we summarize the challenges and prospects faced by bacteria in clinical research, and hope to provide ideas for clinical translation.

Efficacy of low intensity pulsed ultrasound in the treatment of erectile dysfunction / 现代泌尿外科杂志

【Objective】 To investigate the efficacy of low intensity pulsed ultrasound (LIPUS) in the treatment of erectile dysfunction (ED). 【Methods】 A total of 121 ED patients treated during June 2020 and June 2022 were selected as the research objects. According to the International Erectile Index Score (IIEF-EF), the patients were divided into three subgroups:mild (17-25 points), moderate (11-16 points), and severe (0-10 points). The total effective rate, erectile hardness scale (EHS), sex life log questions (SEP), general assessment questionnaire (GAQ), peak systolic velocity (PSV), end diastolic velocity (EDV), and adverse reactions of the three groups before treatment, 4 weeks and 12 weeks after treatment were analyzed. 【Results】 A total of 119 patients completed the follow-up. There were significant increases in IIEF-EF and EHS at week 4 and 12 (P<0.05), and the total effective rate was 69.75% and 76.47%, respectively. The total effective rate was significantly higher in the mild and moderate groups than in the severe group at week 4 and 12 (P<0.05). The patients who answered "yes" to SEP2 and SEP3 accounted for 91.60% and 71.43%, respectively at week 4, and 92.44% and 78.15% at week 12, both significantly higher than the rates before treatment (52.10% and 27.73%, P<0.05). The proportion of patients who answered "yes" to GAQl and GAQ2 at week 4 were 84.87% and 71.43%, respectively, and were 82.35% and 70.59% respectively at week 12, with no significant difference. The PSV level significantly increased at week 12 compared to that before treatment [(48.85±14.11) cm/s vs. (41.42±14.90) cm/s] (P<0.05), while the EDV level significantly decreased [(-0.57±7.01) cm/s vs. (2.25± 5.68)cm/s] (P<0.05). 【Conclusion】 LIPUS can improve erectile function in ED patients without obvious adverse reactions.

The role of SUMOylation in the protective mechanisms of therapeutic hypothermia on neonatal hypoxic-ischemic encephalopathy / 中国新生儿科杂志

Objective:To study the role of SUMOylation in the process of therapeutic hypothermia on neural stem cells (NSCs) in neonatal hypoxic-ischemic encephalopathy.Methods:SUMOylation is an essential post-translational modification involving small ubiquitin-like modifiers (SUMOs). Primary-cultured NSCs from mice were assigned into four groups: control group, hypoxia group, hypothermia group and hypoxia+hypothermia group. Western Blot was used to detect the protein levels of SUMO2/3, hypoxia-inducible factor-1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator factor 1α (PGC-1α) and octamer binding transcription factor 4 (Oct4). The diameters of NSCs were compared. ELISA was used to detect lactate dehydrogenase (LDH) level. Apoptosis was examined using flow cytometry. Immunofluorescence method was used to measure the differentiation of NSCs into neuronal cells.Results:Compared with the control group, the levels of SUMO2/3, HIF-1αand PGC-1α in NSCs of the hypoxia group increased 33%, 126% and 140%, respectively ( P<0.05). Compared with the control group, the levels of SUMO2/3 and PGC-1α in NSCs of the hypothermia group increased 52% and 536%, respectively ( P<0.05). Compared with the hypoxia group, the levels of SUMO2/3, HIF-1α, PGC-1α and Oct4 in the hypoxia+hypothermia group increased 44%, 40%, 230% and 59%, respectively ( P<0.05). The diameters of NSCs in hypoxia group, hypothermia group and hypoxia+hypothermia group were smaller than control group, and hypoxia+hypothermia group smaller than hypoxia group ( P<0.05). No significant differences existed in LDH levels between hypothermia group and control group ( P>0.05). LDH level in hypoxia+hypothermia group were significantly lower than hypoxia group ( P<0.05). No significant differences existed in the cell death rates between hypothermia group and control group ( P>0.05). The cell death rate in hypoxia+hypothermia group was significantly lower than hypoxia group ( P<0.05). Compared with the control group, the expressions of Nestin in both hypoxia group and hypothermia group were increased, but neuron specific enolase (NSE) were decreased ( P<0.05). Compared with hypoxia group and hypothermia group, the level of Nestin in hypoxia+hypothermia group was further increased, while NSE was further decreased ( P<0.05). Conclusions:Therapeutic hypothermia may increase the tolerance of NSCs to hypoxia by enhancing SUMO modification of proteins, providing theoretical basis for the treatment of hypoxic-ischemic encephalopathy with therapeutic hypothermia.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity / 药物分析学报

Small ubiquitin-related modifier(SUMOylation)is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload.However,the function of SUMOylation after myocardial infarction(MI)and the molecular details of heart cell responses to SUMO1 deficiency have not been determined.In this study,we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI.However,SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury.Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells.Among cardiomyocytes,SUMO1 deletion increased the Nppa+Nppb+Ankrd1+cardiomyocyte subcluster pro-portion after MI.In addition,the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice.Importantly,SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes.Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium.Mice preinjected with cardiomyocyte-specific AAV-SUMO1,but not the endothelial cell-specific form,and exhibited ameliorated cardiac remodeling following MI.Collectively,our results identified the role of SUMO1 in cardiomyocytes,fibroblasts,and endothelial cells after Ml.These findings provide new insights into SUMO1 involvement in the patho-genesis of MI and reveal novel therapeutic targets.

Analysis of chest imaging features of novel coronavirus pneumonia, bacterial pneumonia and viral pneumonia / 中华危重病急救医学

Objective:To investigate and summarize the chest CT imaging features of patients with novel coronavirus pneumonia (COVID-19), bacterial pneumonia and other viral pneumonia.Methods:Chest CT data of 102 patients with pulmonary infection due to different etiologies were retrospectively analyzed, including 36 patients with COVID-19 admitted to Hainan Provincial People's Hospital and the Second Affiliated Hospital of Hainan Medical University from December 2019 to March 2020, 16 patients with other viral pneumonia admitted to Hainan Provincial People's Hospital from January 2018 to February 2020, and 50 patients with bacterial pneumonia admitted to Haikou Affiliated Hospital of Central South University Xiangya School of Medicine from April 2018 to May 2020. Two senior radiologists and two senior intensive care physicians were participated to evaluated the extent of lesions involvement and imaging features of the first chest CT after the onset of the disease.Results:Bilateral pulmonary lesions were more common in patients with COVID-19 and other viral pneumonia, and the incidence was significantly higher than that of bacterial pneumonia (91.6%, 75.0% vs. 26.0%, P < 0.05). Compared with other viral pneumonia and COVID-19, bacterial pneumonia was mainly characterized by single-lung and multi-lobed lesion (62.0% vs. 18.8%, 5.6%, P < 0.05), accompanied by pleural effusion and lymph node enlargement. The proportion of ground-glass opacity in the lung tissues of patients with COVID-19 was 97.2%, that of patients with other viral pneumonia was 56.2%, and that of patients with bacterial pneumonia was only 2.0% ( P < 0.05). The incidence rate of lung tissue consolidation (25.0%, 12.5%), air bronchial sign (13.9%, 6.2%) and pleural effusion (16.7%, 37.5%) in patients with COVID-19 and other viral pneumonia were significantly lower than those in patients with bacterial pneumonia (62.0%, 32.0%, 60.0%, all P < 0.05), paving stone sign (22.2%, 37.5%), fine mesh sign (38.9%, 31.2%), halo sign(11.1%, 25.0%), ground-glass opacity with interlobular septal thickening (30.6%, 37.5%), bilateral patchy pattern/rope shadow (80.6%, 50.0%) etc. were significantly higher than those of bacterial pneumonia (2.0%, 4.0%, 2.0%, 0%, 22.0%, all P < 0.05). The incidence of local patchy shadow in patients with COVID-19 was only 8.3%, significantly lower than that in patients with other viral pneumonia and bacterial pneumonia (8.3% vs. 68.8%, 50.0%, P < 0.05). There was no significant difference in the incidence of peripheral vascular shadow thickening in patients with COVID-19, other viral pneumonia and bacterial pneumonia (27.8%, 12.5%, 30.0%, P > 0.05). Conclusions:The probability of ground-glass opacity, paving stone and grid shadow in chest CT of patients with COVID-19 was significantly higher than those of bacterial pneumonia, and it was more common in the lower lungs and lateral dorsal segment. In other patients with viral pneumonia, ground-glass opacity was distributed in both upper and lower lungs. Bacterial pneumonia is usually characterized by single lung consolidation, distributed in lobules or large lobes and accompanied by pleural effusion.

Effect of proprotein convertase subtilisin/kexin type 9 on platelet activation associated with sepsis / 中华危重病急救医学

Objective:To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis.Methods:① Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. ② Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting.Results:① Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (μg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×10 9/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients ( n = 20) was significantly higher than that in the non-thrombocytopenia patients ( n = 37; μg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients ( r = -0.340, P = 0.010). ② Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×10 9/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/β-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. Conclusion:PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

Analysis of operation efficiency and resource allocation of clinical departments in a hospital based on data envelopment andlysis / 中华医院管理杂志

Objective:To establish a calculation model for the operational efficiency and resource allocation of clinical departments in hospitals, for references for hospitals to optimize resource allocation.Methods:The informations including hospitalization time, nursing grade, etc. of inpatients admitted by 32 clinical departments in a tertiary public hospital from January to December in 2021 were extracted. A data envelopment analysis method was conducted on the operation efficiency and input edundancy of the departments. The K-means algorithm was used to divide inpatients into 3 categories according to the level of medical workload. Taking the numbers of doctors, nurses and beds as the input indicators, and the numbers of patients in the 3 categories as the output indicators, a BCC model 1 was established to evaluate the efficiency of resources invested by clinical departments into professional human value. At the same time, a BCC model 2 was established with the total number of patients admitted and medical income as the output indicators to evaluate the efficiency of resources invested by clinical departments into economic benefits.Results:A total of 38 147 inpatients were enrolled. There were 14 departments with overall technical efficiency (OTE) =1.000 in the BCC model 1, 10 departments with OTE=1.000 in the BCC model 2, and 8 departments with OTE=1.000 in the 2 models. As for the input redundancy, 6 departments had high input redundancy in the BCC model 1, 11 departments had high input redundancy in the BCC model 2, and 4 departments had high input redundancy in both models.Conclusions:The model established by this study could effectively evaluate the operational efficiency and input redundancy of clinical departments, identify departments with high workload and low economic benefits, and provide reference for the rational allocation of medical resources in hospitals.

Inhibitory effect of resveratrol on neovascularization in cutaneous squamous cell carcinoma by suppressing the SUMOylation of hypoxia-inducible factor 1α protein / 中华皮肤科杂志

Objective:To explore intrinsic mechanisms underlying the inhibitory effect of resveratrol on neovascularization in cutaneous squamous cell carcinoma from the perspective of ubiquitin/ubiquitin-like protein modification balance.Methods:The human cutaneous squamous cell carcinoma cell line A431 was used as the research object. Cultured A431 cells at exponential growth phase were divided into 3 groups (control group, 50 μmol/L resveratrol group, and 100 μmol/L resveratrol group) to be cultured with mediums containing 0, 50, and 100 μmol/L resveratrol, respectively. Cell proliferation activity was assessed by the 3- (4,5) -dimethylthiazol (-z-y1) -2,5-di-phenytetrazoliumromide (MTT) assay after 48-hour culture; the vasculogenic mimicry formation assay was performed to evaluate the vasculogenic mimicry formation ability of A431 cells after 12-hour treatment with resveratrol; Western blot analysis was conducted to detect the relative protein expression levels of ubiquitin, small ubiquitin-related modifier-1 (SUMO1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor receptor (VEGFR) in different groups after 48-hour treatment with resveratrol. Then, 24 8-week-old BALB/c male thymectomized mice were randomly and equally divided into 3 groups to be subcutaneously inoculated with A431 cells in the inguinal region, followed by intraperitoneal injections of 1 mg/kg or 2 mg/kg resveratrol (1 mg/kg or 2 mg/kg resveratrol group), or the same volume of physiological sodium chloride solutions (control group) ; the intraperitoneal injections were done once every 3 days in all groups; all the above mice were sacrificed on the 21st day, and the tumors were resected and weighed. Immunohistochemistry assay was performed to determine the CD31 expression in tumor tissues. One-way analysis of variance was used for comparisons among multiple groups, and least significant difference (LSD) - t test was used for multiple comparisons. Results:The proliferation rate of A431 cells significantly differed among the control group, 50 μmol/L resveratrol group, and 100 μmol/L resveratrol group ( F = 17.75, P = 0.017), and was significantly lower in the 50 μmol/L resveratrol group (66.53% ± 5.09%) and the 100 μmol/L resveratrol group (35.88% ± 4.28%) than in the control group (100%, LSD- t = 21.17, 29.04, P = 0.011, 0.004, respectively) ; the total length of vessel wall-like structures formed by A431 cells significantly differed among the 3 groups ( F = 21.37, P = 0.004), and was significantly lower in the 50 μmol/L resveratrol group (102.73 ± 11.36 μm) and the 100 μmol/L resveratrol group (37.83 ± 4.19 μm) than in the control group (185.26 ± 8.02 μm, both P < 0.05) ; the relative protein expression levels of ubiquitin, SUMO1, HIF-1α, and VEGFR also significantly differed among the 3 groups, the ubiquitin protein expression was significantly higher in the 50 μmol/L resveratrol group (2.09 ± 0.13) and the 100 μmol/L resveratrol group (3.53 ± 0.16) than in the control group (0.68 ± 0.11, both P < 0.05), while the protein expression of SUMO1, HIF-1α, and VEGFR was significantly lower in the 50 μmol/L resveratrol group (1.87 ± 0.13, 0.81 ± 0.06, 0.73 ± 0.09, respectively) and the 100 μmol/L resveratrol group (1.02 ± 0.11, 0.45 ± 0.06, 0.39 ± 0.05, respectively) than in the control group (3.10 ± 0.11, 0.97 ± 0.08, 0.98 ± 0.07, respectively, all P < 0.05). In the mice experiment, the weight of subcutaneous tumors and the proportion of CD31-positive cells in tumor tissues significantly differed among the control group, 1 mg/kg resveratrol group, and 2 mg/kg resveratrol group (weight: 3.29 ± 0.57 g, 2.91 ± 0.49 g, 2.55 ± 0.52 g; proportion: 76.24% ± 5.51%, 39.45% ± 5.48%, 12.07% ± 3.54%; F = 14.33, 15.34, P = 0.019, 0.021, respectively), and were significantly lower in the 1 mg/kg resveratrol group and 2 mg/kg resveratrol group than in the control group (all P < 0.05) . Conclusion:Resveratrol could inhibit tumor growth and neovascularization in tumor tissues, which were possibly associated with the inhibitory effect of resveratrol on neovascularization in cutaneous squamous cell carcinoma by suppressing the SUMOylation of HIF-1α protein via ubiquitin/ubiquitin-like protein modification pathways.

Perspective of radiotherapy for ovarian metastasis from small cell lung cancer / 西安交通大学学报(医学版)

【Objective】 To evaluate the therapeutic value of radiotherapy for ovarian metastasis from small cell lung cancer. 【Methods】 Two patients with ovarian metastasis from small cell lung cancer were recruited, and the value of radiotherapy in the system treatment strategies was analyzed combined with literature reports. 【Results】 The two patients both benefited from local radiotherapy plus system treatment. One was still in complete remission, and compared to that reported in the literature, the local PFS improved to 21 months. 【Conclusion】 Although the prognosis of small cell lung cancer with ovarian metastasis is still poor, radiotherapy might be one of the systematic treatment strategies for improving the survival time of these patients.

The modified Valsalva maneuver in hypopharynx CT scan / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the significance and factors influencing of CT scan under the modified Valsalva maneuver. Methods:Clinical data of 52 patients with hypopharyngeal carcinoma diagnosed from August 2021 to December 2022 were collected, all patients had calm breathing CT scan and modified Valsalva maneuver CT scan. Compare the exposure effect of the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall, and glottis with each CT scanning method. The effects of age, neck circumference, neck length, BMI, tumor site, and T stage on the exposure effect were analyzed. Results:In 52 patients, 50 patients（96.15%） completed CT scan at once time. The exposure effect of the CT scan under modified Valsalva maneuver in the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall was significantly better than CT scan under calm breathing（Z=-4.002, -8.026, -8.349, -7.781, -8.608, all P<0.01）, while CT scan under modified Valsalva maneuver was significantly worse in glottis than CT scan under calm breathing（Z=-3.625, P<0.01）. In the modified Valsalva CT scan, age had no obvious effect on the exposure effect. The exposure effect was better with long neck length, smaller neck circumference, smaller BMI and smaller T stage. The exposure of postcricoid carcinoma was better than pyriform sinus carcinoma and posterior hypopharyngeal wall carcinoma. But differences were not all statistically significant. Conclusion:The anatomical structure of the hypopharynx was clearly under CT scan with modified Valsalva maneuver, which clinical application is simple, but the effect of glottis was worse. The influence of age, neck circumference, neck length, BMI, and tumor T stage on the exposure effect still needs further investigation.

Summary of 4 cases of minimally invasive tracheotomy for severe pneumonia under extracorporeal membrane oxygenation / 中国中西医结合急救杂志

Objective To summarize the experience of minimally invasive tracheotomy under veno-venous extracorporeal membrane oxygenation(VV-ECMO)in 4 cases of severe pneumonia,and to provide examples for airway management of severe pneumonia patients.Methods A retrospective study method was conducted.Four cases of severe pneumonia patients who underwent extracorporeal membrane oxygenation(ECMO)at the intensive care unit(ICU)of Shandong Provincial Hospital Affiliated to Shandong First Medical University from November 2022 to March 2023 were selected as the study subjects,clinical data on the general conditions,imaging examinations before and after admission to ICU,changes in biochemical indexes before and after ECMO technique,and the performance of bedside minimally invasive tracheotomy were collected.Bedside tracheotomy was performed to assist ventilation for patients according to the change of condition.The changes and prognosis of the patients were observed.Results Four patients with severe pneumonia were treated with bedside tracheotomy-assisted ventilation in the state of continuous VV-ECMO,the oxygen saturation was maintained between 0.98-1.00,the airway was cleared and sputum evacuation was smooth,the vital signs were stable after the operation,and the machine was gradually withdrawn.Conclusion During the treatment of severe pneumonia,the safe and rapid completion of bedside minimally invasive tracheotomy in patients with severe pneumonia under continuous VV-ECMO is a new challenge shared by doctors and nurses of otorhinolaryngology,head and neck surgery,and critical care emergency care unit.The four successful cases of bedside tracheotomy after VV-ECMO treatment we report suggest that bedside minimally invasive tracheotomy can safely and rapidly assist airway management,and may provide more useful experiences for the treatment of severe pneumonia and possible new acute respiratory infectious diseases in the future.

Clinical features and surgical treatment of abdominal unicentric Castleman's disease / 中华普通外科杂志

Objective:To summarize the clinical manifestations, diagnosis and surgical treatment of abdominal unicentric Castleman's disease.Methods:The clinical data of abdominal unicentric Castleman's disease cases admitted to the General Surgery Department of the First Affiliated Hospital,Nanjing Medical University from Jan 2009 to Dec 2019 was retrospectively analyzed.Results:A total of 18 patients were included with definite pathological diagnosis. The main complaint was abdominal pain and discomfort (50%, 6/12), dizziness and fatigue (25%, 3/12), multiple rash with oral ulcer (16.7%, 2/12) and weight loss (8.3%, 1/12). All patients received surgical resection. Postoperative pathology showed clear vascular type in 15 patients and plasma cell type in 3 patients. There were no major complications nor mortality.Conclusion:Abdominal unicentric Castleman's disease has diverse clinical manifestations, which was difficult for preoperative diagnosis, postoperative prognosis is satisfactory.

Control study of the intelligent calculation method and the traditional calculation method in risk assessments of hospitalization / 中华危重病急救医学

Objective:To explore the accuracy of intelligent calculation (IC) method for risk assessment of hospitalization for patients, aiming to build a more advantageous risk assessment system.Methods:The "Search Engine" program was developed based on hospital information system (HIS) of the Fifth Center Hospital in Tianjin, which automatically captured patient information and generated nutritional risk screening 2002 (NRS 2002) score, Caprini thrombosis risk assessment model and Padua thrombosis risk assessment model for venous thromboembolism (VTE), the CHA 2DS 2-VASc for predicting stroke risk stratification in atrial fibrillation and the HAS-BLED for predicting bleeding risk in anticoagulated patients with atrial fibrillation. A randomized controlled trial was conducted. According to the applicable conditions of each risk assessment, 100 risk scores from "Search Engine" program belonged to each risk assessment were randomly selected, defined as the IC group. Manual scoring with the data of the same case at the same time, defined as the traditional calculation (TC) group, compared the consistency of the scores and the difference in time-consuming between the two groups. Results:The Bland-Altman plots showed that the 95% limits of agreement (95% LoA) of NRS 2002 score, Caprini score, Padua score, CHA 2DS 2-VASc score and HAS-BLED score was -0.46 to 0.41, -0.49 to 0.52, -0.50 to 0.41, -0.67 to 0.60, -0.44 to 0.43, respectively, all P > 0.05. In this study, the Bland-Altman plot showed that 95%, 96%, 97%, 97%, 95% plots fell within the 95% LoA in NRS 2002 score, Caprini score, Padua score, wwCHA 2DS 2-VASc score and HAS-BLED score by the two methods, respectively. The all plots of 95% LoA were within the clinically acceptable range (-0.5 to 0.5 scores). The time-consuming of NRS 2002 score, Caprini score, Padua score, CHA 2DS 2-VASc score and HAS-BLED score in IC group were significantly shorter than those in TC group [0.72 (0.71, 0.73) seconds vs. 361.02 (322.41, 361.02) seconds, 0.72 (0.72, 0.73) seconds vs. 196.68 (179.99, 291.20) seconds, 0.72 (0.72, 0.73) seconds vs. 105.75 (92.32, 114.70) seconds, 0.72 (0.71, 0.72) seconds vs. 72.66 (56.24, 84.20) seconds, 0.72 (0.71, 0.72) seconds vs. 51.30 (38.88, 57.15) seconds, respectively, all P < 0.001]. Conclusion:For the above five risk assessments, the TC method and IC method has good consistency in scores, and the IC method is faster, which has good application prospect for clinical application.

Prognostic value of PCSK9 and blood lipid in patients with sepsis / 中华危重病急救医学

Objective:To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis.Methods:Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn.Results:There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [μg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [μg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95% CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (β value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 μg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. Conclusions:PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 μg/L, the 28-day survival rate decreased significantly.

Mechanism of high mobility group protein B1 in lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome / 中华危重病急救医学

Objective:To investigate the role and possible pathogenesis of high mobility group protein B1 (HMGB1) in lipopolysaccharide (LPS)-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS).Methods:① In vivo, 24 SPFC57BL/6 male mice were randomly divided into normal control group, ALI/ARDS model group, ethyl pyruvate (EP) treatment group and EP control group, with 6 mice in each group. The ALI/ARDS model was established by intraperitoneal injection of 20 mg/kg LPS. Mice in normal control group and EP control group were intraperitoneally injected with the same amount of sterile normal saline. Then, mice in the EP treatment group and EP control group were intraperitoneally injected with 40 mg/kg HMGB1 inhibitor EP. After 6 hours, the mice were sacrificed and lung tissues were collected. The expressions of heparan sulfate (HS), syndecans-1 (SDC-1), heparanase (HPA) and matrix metalloproteinases-9 (MMP-9) in lung tissues were detected by immunofluorescence technique. Orbital blood of mice was collected and serum was extracted to detect the content of HMGB1 by enzyme linked immunosorbent assay (ELISA). ② In vitro, human umbilical vein endothelial cells (HUVECs) were randomly divided into 6 groups: normal control group, HUVECs damage group (treated with 1 mg/L LPS for 6 hours), HMGB1 group (treated with 1 μmol/L recombinant HMGB1 for 6 hours), HMGB1+EP group (treated with recombinant HMGB1 for 1 hour and then added 1 μmol/L EP for 6 hours), LPS+EP group (treated with LPS for 1 hour and then added 1 μmol/L EP for 6 hours), EP group (treated with 1 μmol/L EP for 6 hours). The expressions of HS, SDC-1, HPA and MMP-9 in endothelial cells were detected by immunofluorescence technique. Results:① In vivo, light microscopy showed that the alveolar space was thickened after LPS stimulation, and there were a large number of inflammatory cells infiltrating in the alveolar space. Compared with ALI/ARDS model group, the expressions of HS and SDC-1 in lung tissue of EP treatment group were significantly increased [HS (fluorescence intensity): 0.80±0.20 vs. 0.53±0.02, SDC-1 (fluorescence intensity): 0.72±0.02 vs. 0.51±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly decreased [HPA (fluorescence intensity): 2.36±0.05 vs. 3.00±0.04, MMP-9 (fluorescence intensity): 2.55±0.13 vs. 3.26±0.05, both P < 0.05]; there were no significant changes of the above indexes in EP control group. Compared with ALI/ARDS model group, the content of serum HMGB1 in EP treatment group decreased significantly (μg/L: 131.88±16.67 vs. 341.13±22.47, P < 0.05); there was no significant change in the EP control group. ② In vitro, compared with HMGB1 group, the expressions of HS and SDC-1 in HMGB1+EP group were significantly higher [HS (fluorescence intensity): 0.83±0.07 vs. 0.56±0.03, SDC-1 (fluorescence intensity): 0.80±0.01 vs. 0.61±0.01, both P < 0.05], and the expressions of HPA and MMP-9 were significantly lower [HPA (fluorescence intensity): 1.30±0.02 vs. 2.29±0.05, MMP-9 (fluorescence intensity): 1.55±0.04 vs. 2.50±0.06, both P < 0.05]; the expression of HS, SDC-1, HPA and MMP-9 had no significant changes in EP group. Conclusion:HMGB1 participates in LPS-induced injury of endothelial cell glycocalyx, leading to increased lung permeability, and inhibition of HMGB1 can alleviate lung injury.

Changes of ferroptosis in hippocampal neurons of rats with multiple cerebral concussion / 中华行为医学与脑科学杂志

Objective:To observe the ferroptosis in hippocampal neurons of rats with multiple cerebral concussion (MCC) .Methods:Ninety clean grade male Wistar rats with a body mass of (250±10) g were randomly divided into control group (12 rats) and model group (78 rats) according to the random number table method. The rat of MCC model was prepared by hitting the frontotemporal lobe of rats with free fall method once a day for 3 consecutive days.Then the MCC model rats were randomly divided into 12 h, 24 h, 48 h, 72 h, 7 d and 14 d groups with 12 rats in each group. The balance beam experiment was used to detect the motor coordination function of the rats. The levels of interleukin-β(IL-1β), interleukin-6(IL-6), serum glutathione (GSH), neuron-specific enolase (NSE) in serum of rats were detected by ELISA.The content of iron ion in hippocampus was detected by colorimetry. The mRNA and protein levels of glutathione peroxidase 4(GPX4), ferritin heavy (FTH) and ferritin light(FTL) in the hippocampus were detected by RT-PCR and Western blot. Prussian blue staining was used to observe the iron deposition in brain tissue.The ultrastructural changes of hippocampal neurons and mitochondria were observed by transmission electron microscope. SPSS 24.0 statistical software was used for one-way ANOVA among groups, and LSD test was used for multiple pairwise comparison.Results:In the balance beam experiment, the passing time and motor coordination score of rats in each group were significantly different ( F=30.08, 60.34, both P<0.05). The passing time and motor coordination score of rats in the 48 h group ((87.00±4.74) s, (4.75±0.43)) were significantly higher than those in the control group ((35.13±6.99) s, (0.75±0.23)) (both P<0.05). There was significant difference in the total iron ion content, Fe 2+ content and Fe 3+ content in hippocampus of rats in each group ( F=25.20, 94.42, 40.25, all P<0.05), and the content of Fe 2+ in hippocampus of 48 h group was significantly higher than that of the control group ((10.17±0.05) ng/μL, (8.65±0.01) ng/μL)( P<0.05). In the results of RT-PCR and Western blot, the mRNA and protein levels of GPX4, FTH and FTL in hippocampus of each group were significantly different ( F=37.94, 82.09, 49.01, 71.63, 28.94, 15.78, all P<0.05). The mRNA level and protein level of GPX4 ((1.09±0.01), (0.23±0.01) )and FTL ((1.60±0.03), (0.64±0.02)) in 24 h group were significantly higher than those of the control group (GPX4: (1.00±0.02), (0.17±0.01)), FTL: ((1.00±0.04), (0.32±0.01))(all P<0.05). The mRNA level and protein level of FTH ((0.24±0.03), (0.07±0.01)) in 24 h group were significantly lower than those of the control group((1.00±0.01), (0.67±0.03))(both P<0.05). The results of electron microscope showed that the hippocampal neuronal cells of the model rats were reduced, the nucleolus was broken and the nuclear membrane was shrunk in varying degrees, the mitochondria were swollen and deformed and there were vacuoles, and the cristae in the mitochondria decreased or disappeared. Conclusion:The levels of inflammatory reaction and oxidative stress in the multiple cerebral concussion model rats increase, and the hippocampal neurons show the characteristics of ferroptosis, especially at 24 h and 48 h.